This invention relates to ion sensors, more specifically electrodes having an ion-selective membrane in direct contact with an electrical conductor.
Potentiometric assays of a specific ionic species in solutions containing other ions are well known in the art, and employ electrodes with a known response to the concentration of the ion to be assayed. Such electrodes are commonly termed ion-selective electrodes. In one class of such ion-selective electrodes, membranes having selective permeability to the ionic species to be assayed interface between the solution to be analyzed and the conductive member of the electrode. Among the types of material which have been used to form ion-selective membranes are ion-selective glass, ion-selective polymer and ion-selective water-immiscible liquid.
The ion-selective electrode is used in conjunction with a reference electrode to form an electrochemical cell by immersion in the solution to be analyzed. The potential which develops across this cell is proportional to the logarithm of the activity or the concentration in the solution of the ions to which the ion-selective electrode is sensitive. This potential is detected by an electromeric device, usually either a direct reading circuit or a null-balance potentiometric circuit.
Coated-wire electrodes are a type of ion selective electrode formed by coating a metallic wire or other electrical conductor with a polymeric ion selective membrane. They do not in general employ an internal reference electrode element, but membranes used on them can also be used on electrodes employing such an internal reference element. Coated wire electrodes and their preparation are described in detail by R. W. Cattrall and I. C. Hamilton in the article "Coated-Wire Ion-Selective Electrodes", Ion-Selective Electrode Rev., 1984, Vol. 6, pp. 125-172, incorporated herein by reference to the extent that it is pertinent. U.S. Pat. No. 4,948,473 also describes preparation of coated-wire electrodes and is incorporated herein by reference to the extent that it is pertinent.
The Nikolskii-Eisenman extension of the Nernst equation correlates electomotive force (EMF) or the measured potential with the activity or concentration of the specific ion in solution which can permeate the ion-selective membrane, in the presence of an interfering ion. This equation and an explanation of it are given by U. Oesch, D. Ammann and W. Simon in an article in the publication "Clinical Chemistry", 32/8, 1448-1459 (1986), which is incorporated herein by reference.
Ideally, for the specific ion, in a solution with other ions, for which an ion-selective electrode has exclusive selectivity, a plot of the negative logarithm of the concentration or activity of this species versus the measured potential in millivolts (mV) gives a straight line, which for monovalent ions has a theoretical slope of 59.2 at 25.degree. or 58.degree. at 20.degree. C. Sensitivity to a specific ionic species is defined as the concentration range of the specific ionic species within which this relationship remains linear. The wider the linear response range of an ion-selective electrode, the more reliable and precise will be assays of the specific ionic species it detects.
Membrane forming phospholipids have been used as discrete layers in the construction of ion selective electrodes of various types. McConnell in U.S. Pat. 4,490,216 cites the use of bilayer forming phospholipids as the second layer of a membrane in an electroanalytical device. Krull et al in U.S. Pat. 4,637,861 discloses means to chemically anchor membrane forming phospholipid derivatives to oxidized electrolytic glassy carbon surfaces. Janata in U.S. Pat. No. 4,776,944 discloses a multi-layered active electrode in which selectivity is provided by either a natural lipid bilayer film obtained from plants or animals or a synthetic phospholipid film produced by the Langmuir-Blodgett process, either of which would include "gating" molecules which control the "opening" and "closing" of the film to the transport of ions.
In all cases of the above art, an effort is made to form an electrode in which the benefits of the phospholipid are derived from deliberately creating a discrete phospholipid monolayer or bilayer or maintaining such a structure originally derived from a plant or animal source.
Commercial application of coated wire electrodes and other electrodes employing an ion-specific polymeric membrane, for example, in the detection of ions in physiological fluids, environmental samples and in test kits intended for non-professional use, is restricted by a lack of reliability of the assay results. A critical cause of this lack of reliability is the failure of the linear detection range to extend far enough into the low concentrations which are of interest in the assay of for example, biological fluids, thereby reducing the accuracy and precision of the measurement.
An additional problem with electrodes of the coated wire type is mechanical instability of the ion selective membrane due to poor adhesion to the underlying conductive member.
Another factor impeding commercial application of coated wire electrodes is the lack of a simple, economical commercial process for their manufacture which reliably produces ion-specific electrodes with the same linear response range to a specific ion. Although coated wire electrodes are generally easier to prepare than conventional electrodes such as the barrel type, many steps are required and there may be significant variation in sensitivity and precision of electrodes both within and between batches detracting from the efficiency of commercial production.
Limited shelf life and operational lifetime also restrict the commercial utility of such electrodes.
A further problem preventing wider use of coated wire ion-selective electrodes is that they are too difficult for use by lay personnel. For example, ion-specific electrodes having linear response over a relatively narrow range are more complicated to calibrate than whose response is linear over a wide range.
Yet another problem with existing coated wire electrodes prepared by present processes is difficulty in achieving an optimally miniaturized configuration of the active electrode site.
For the foregoing reasons there is a need for ion-selective electrodes with wide linear response range which can be easily miniaturized and used and a process to produce them inexpensively with a high degree of reliability and consistency.